Sakuranin represses the malignant biological behaviors of human bladder cancer cells by triggering autophagy via activating the p53/mTOR pathway

BMC Urology

Research

Haitao Mu¹  Ling Hao²  Dandan Mu³ 

[1] Department of Medical Oncology, The Fifth Hospital of Harbin, Harbin, China;Department of Medical Oncology, The Fourth Affiliated Hospital of Harbin Medical University, No.37, Yiyuan Street, 150000, Harbin, China;Department of Medical Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China;

关键词: Sakuranin;    Bladder cancer;    T24 cells;    Autophagy;    p53/mTOR pathway;    Proliferation;    Apoptosis;   

DOI  :  10.1186/s12894-023-01334-2

 received in 2023-02-17, accepted in 2023-10-03,  发布年份 2023

来源: Springer

【 摘 要 】

ObjectiveSakura extract is a natural flavonoid compound that may have potential anti-tumor effects. The paper focuses on investigating Sakuranin mechanism on bladder cancer (BC) cells.MethodsBC cells (T24) were treated with different concentrations of Sakuranin, with 48-h IC50 determined. T24 cells were treated with Sakuranin at IC50, followed by assessment of cell proliferative/apoptotic/migrative/invasive activities by CCK-8, EdU and plate clone formation assays/flow cytometry/Transwell/scratch test. MMP-2 (migration and invasion-related protein) protein level was assessed by Western blot. Cell autophagy was evaluated by measuring the protein levels of autophagy markers (LC3-I/LC3-II/p62) through Western blot. The autophagy inhibitor 3-MA was used to validate the role of autophagy in the regulatory mechanism of Sakuranin in T24 cell behaviors. Furthermore, the activation of the p53/mTOR pathway in cells was detected and a combination of Sakuranin and p53 inhibitor Pifithrin-µ was adopted to explore the involvement of this pathway.ResultsSakuranin decreased T24 cell proliferation/EdU positive cell percentage/colony formation number and area/migration/invasion/scratch healing/MMP-2 protein level, and accelerated apoptosis. Sakuranin elevated the LC3-II/I ratio and lowered p62 level in T24 cells. 3-MA partially averted Sakuranin-mediated repression on cell malignant behaviors. Sakuranin upregulated p-p53 and p53 levels, and decreased the p-mTOR/mTOR ratio in T24 cells. The effects of Sakuranin on cell biological behaviors were partly annulled by Pifithrin-µ treatment.ConclusionSakuranin suppressed T24 cell proliferation/migration/invasion, and enhanced apoptosis by potentiating autophagy through activating the p53/mTOR pathway. This study provided a theoretical basis for Sakuranin as a potential drug for clinical treatment of BC.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 4

12951_2015_155_Article_IEq78.gif

Fig. 2

Fig. 4

Fig. 2

Fig. 6

Fig. 1

12951_2016_246_Article_IEq1.gif

Fig. 3

Fig. 1